There is an unmet need for cost-efficient technologies for high-purity isolation and analysis of cells in animal blood and tissue solutions. The prior art describes several methods for isolating these cells through centrifugation and through the application of magnetic force. Other methods of cell isolation also include use of microfluidics, filtration, and others.
Centrifugation, the use of centrifugal force for the sedimentation of heterogeneous mixtures with a centrifuge, is a common method for isolating cells in animal blood. The prior art describes a number of centrifuge apparati, but these apparati are expensive and complex, such that, primarily, only laboratories can afford them, and only laboratory technicians can operate them. This limits the clinical and consumer applications of centrifugal isolation. Furthermore, centrifugation-based methods separate cells based on physical properties (e.g. density, size, shape), and do little to separate cell based on protein expression and biochemical profile.
Magnetic force is an alternative to centrifugal force for isolating cells in animal blood. An example of this application from the prior art is the use of immunomagnetic nanobeads and lateral magnetophoresis for isolation of circulating tumor cells (CTC's). While effective, the application of this isolation method is costly and requires the expertise of a laboratory-trained technician. This limits the clinical and consumer applications of magnetic force isolation.
Centrifugal and magnetic force isolation of cells in animal blood entails infusing the cells in a solution causing them to fall. An innovation is to use microbubbles with selection markers adjacent thereto for cell isolation. Microbubbles are bubbles less than can be less than a millimeter in diameter to greater than a micrometer in diameter. Microbubbles can be filled inside with a gas, such as air or perfluorocarbon. Adjacent to cells or other biological agents or non-biological agents, microbubbles can cause those agents to float in a liquid. In some instances, biological or non-biological agents can float in the presence or absence of microbubbles adjacent thereto by including a liquid or gas, or combination thereof, that cause the agents to float, such as solutions that are known in the art. In some instances, the microbubbles, adjacent thereto biological agents or non-biological agents that are isolated or enriched, are disrupted.
Generally, cells with microbubble adjacent thereto are placed into standard centrifuge tubes for the application of centrifugal or magnetic force for isolation or enrichment. The prior art uses certain inverted tubes and other container apparati to increase microbubble effectiveness, but none of these apparati allow for the isolation of cells absent a centrifugal force, and a laboratory-trained technician to properly apply this force to the agents. This creates high costs and inefficient isolation results.
These high costs and inefficient results limit the application of the prior art's isolation methods. Large research institutions, along with well-funded private companies, can afford to apply these isolation methods, but smaller entities or personal or consumer users and clinics lacking laboratory equipment and know-how, cannot. Furthermore, the prior art has no practically implementable consumer applications, as ordinary consumers lack the level of skill needed to operate a centrifuge or a magnetic force application, and the resources needed to purchase expensive equipment.
While the prior art illustrates methods and devices for improving existing cell isolation techniques, it provides no viable alternative for isolating cells, whether microbubble-adjacent thereto or not, without the application of centrifugal or magnetic force, and the necessary laboratory expenses and know-how to apply such forces. Life-saving applications of isolating cells from animal blood, in clinical and consumer environments, are limited as a result.
Cells from animal blood are not the only biological agents isolated through centrifugal and magnetic force technology. Other potentially life-saving applications include the isolation of cells (such as stem cells, immune cells, circulating tumor cell cells (CTC's), tumor cells, or other cells), cell fragments, bacteria, viruses, parasites, and others. The development of alternatives to centrifugal and magnetic force for isolating biological agents is critical in order to apply the life-saving properties of those isolated biological agents to the home and to the clinic.